Subclinical Status Epilepticus Research Articles

Early Subclinical Status Epilepticus May Contribute to Developmental Delays in Infants With Tuberous Sclerosis Complex

We present a case of a newborn with a prenatally discovered cardiac rhabdomyoma leading to early genetic diagnosis of tuberous sclerosis complex (TSC). This early diagnosis prompted a presymptomatic electroencephalography (EEG) that revealed subclinical seizures meeting the definition for status epilepticus on day 1 of life. Antiseizure medications (ASMs), including vigabatrin, were started. The EPISTOP and PREVeNT trials demonstrated that early life initiation of vigabatrin may reduce the degree of refractory epilepsy and epileptic spasms (ES) in this population (TSC). Although neonatal seizures are a known entity in TSC, continuous neonatal EEG monitoring is not standard at birth. This case supports early consideration for neonatal EEG monitoring to identify and treat neonatal seizures, reduce risk for infantile spasms, and potentially improve neurodevelopmental outcomes.

Brain Injury in Critical Illness and a Note on the Virus

Brain Injury in Critical Illness and a Note on the Virus

DIagnostic Subdural EEG electrodes And Subdural hEmatoma (DISEASE): a study protocol for a prospective nonrandomized controlled trial

BackgroundEpileptic seizures are common clinical features in patients with acute subdural hematoma (aSDH); however, diagnostic feasibility and therapeutic monitoring remain limited. Surface electroencephalography (EEG) is the major diagnostic tool for the detection of seizures but it might be not sensitive enough to detect all subclinical or nonconvulsive seizures or status epilepticus. Therefore, we have planned a clinical trial to evaluate a novel treatment modality by perioperatively implanting subdural EEG electrodes to diagnose seizures; we will then treat the seizures under therapeutic monitoring and analyze the clinical benefit.MethodsIn a prospective nonrandomized trial, we aim to include 110 patients with aSDH. Only patients undergoing surgical removal of aSDH will be included; one arm will be treated according to the guidelines of the Brain Trauma Foundation, while the other arm will additionally receive a subdural grid electrode. The study’s primary outcome is the comparison of incidence of seizures and time-to-seizure between the interventional and control arms. Invasive therapeutic monitoring will guide treatment with antiseizure drugs (ASDs). The secondary outcome will be the functional outcome for both groups as assessed via the Glasgow Outcome Scale and modified Rankin Scale both at discharge and during 6 months of follow-up. The tertiary outcome will be the evaluation of chronic epilepsy within 2–4 years of follow-up.DiscussionThe implantation of a subdural EEG grid electrode in patients with aSDH is expected to be effective in diagnosing seizures in a timely manner, facilitating treatment with ASDs and monitoring of treatment success. Moreover, the occurrence of epileptiform discharges prior to the manifestation of seizure patterns could be evaluated in order to identify high-risk patients who might benefit from prophylactic treatment with ASDs.Trial registrationClinicalTrials.gov identifier no. NCT04211233.

109 Rapid Response Electroencephalograph With Artificial Intelligence for Diagnosing Seizures and Highly Epileptiform Patterns in Emergency Medicine

To test the performance of a recently FDA-cleared machine learning method (Claritγ) that generates bedside alerts for possible status epilepticus and measures in real time the burden of seizure activity. We designed a retrospective study of electroencephalographs from adult patients (n=353) who underwent monitoring with Rapid Response EEG system (Rapid-EEG, Ceribell Inc.) for evaluation of possible seizures between January 2018 and April 2019. We developed a machine learning method for automated detection of seizure activity and seizure burden throughout each recording. We measured sensitivity and specificity of possible status epilepticus (seizures>5 minutes) and real-time seizure burden measurements generated by Claritγ compared to the majority consensus of at least 2 expert neurologists reviewing the same EEGs. Various thresholds of seizure burden were tested (≥10% indicating at least 30 seconds seizure activity in the last 5 minutes, ≥50% indicating at least 2.5 minutes of seizure activity, and ≥90% indicating at least 4.5 minutes of seizure activity and triggering an alert for status epilepticus). Majority consensus of neurologists labeled the 353 EEGs as normal or slow activity (n=249), highly epileptiform patterns (HEP, n=87), or seizures (N=17, nine longer than five minutes and eight shorter than five minutes). The sensitivity and specificity of various thresholds for seizure burden during EEG recordings for detecting patients with seizures was 100% and 82% for 50% seizure burden and 88% and 60% for 10% seizure burden. The algorithm generated a status epilepticus alert (≥90% seizure burden) with 100% sensitivity and 93% specificity. Of the 179 EEG recordings in which the algorithm detected no seizures, seizures were identified by the expert reviewers in only 2 cases, indicating a negative predictive value of 99%. Combination of high sensitivity for status epilepticus events combined with a high negative predictive value for negative cases makes our novel algorithm a useful tool for triaging EEGs in emergency care settings. Confirming cases of non-convulsive subclinical status epilepticus cases within minutes of their arrival to emergency department and independently from neurologists and or EEG technicians will expedite the triage of these critically ill patients and will expedite their treatment. In addition, ruling out seizures accurately in cases being suspected to have seizures can help prevent unnecessary or aggressive over-treatment of such patients.

Case 250: Alpers-Huttenlocher Syndrome.

History A 10-year-old girl with global developmental delay and attention deficit hyperactivity disorder was transferred from an outside hospital because of confusion and multiple episodes of left face and arm jerking. Physical examination revealed normal muscle bulk, strength, and tone in the bilateral upper and lower extremities but insuppressible left arm and jaw twitching Lumbar puncture revealed no white or red blood cells, a normal glucose level of 55 mg/dL (3.0 mmol/L) (normal range, 50-80 mg/dL [2.8-4.4 mmol/L]), and an elevated protein level of 81.6 mg/dL (normal range, 15-60 mg/100 dL). A comprehensive metabolic panel revealed lactic acidosis. The patient was initially started on levetiracetam, phenobarbital, phenytoin, and topiramate for status epilepticus. Hepatic dysfunction was not present at initial admission but developed 2 months later, with an alanine aminotransferase level of 90-406 U/L (1.5-6.8 μkat/L) (normal range, 8-37 U/L [0.13-0.62 μkat/L]) and aspartate aminotransferase in the range of 75-187 U/L (1.2-3.1 μkat/L) (normal range, 8-35 U/L [0.13-0.58 μkat/L]). Electroencephalography revealed right parietal and occipital spike-and-wave discharges, with bursts of up to 20 seconds, which were indicative of subclinical status epilepticus. The family history was remarkable for a sister with head lag, developmental delay, seizure disorder, and liver failure.

Severe Respiratory Acidosis in Status Epilepticus as a Possible Etiology of Sudden Death in Lesch-Nyhan Disease: A Case Report and Review of the Literature.

Lesch-Nyhan disease (LND) is an X-linked disorder of purine metabolism, associated with self-mutilation, dystonia, and chorea. Seizures are uncommon in LND. Patients with LND are at risk for sudden and unexpected death. The etiology of this is unknown, but appears to occur from a respiratory process. We propose that respiratory failure secondary to subclinical seizure may lead to sudden death in these patients. We report a case of an 11-year-old boy with LND who had two episodes of nocturnal gasping. The second event was immediately followed by a 10min generalized seizure. Upon arrival at the hospital, an arterial blood gas test revealed a severe respiratory acidosis. Following aggressive treatment of his seizures, this patient did well, and was discharged home on oxcarbazepine with rectal diazepam. No further seizures have been noted in 1 year of follow-up. In this case report and review, we hypothesize that sudden death from respiratory failure in Lesch-Nyhan disease may in some cases be due to seizure-induced respiratory failure, akin to sudden unexpected death in epilepsy (SUDEP). We suggest screening for paroxysmal respiratory events; consideration of electroencephalography for patients with LND presenting in respiratory distress or failure; and consideration of more aggressive treatment of seizures in these patients. Brief Summary:We present an 11-year-old boy with Lesch-Nyhan disease (LND) who developed respiratory failure and severe respiratory acidosis from his first known seizure, which evolved to subclinical status epilepticus. We propose that patients with LND have a predisposition to respiratory failure and sudden death, which in some cases may be provoked by seizure (sudden unexpected death in epilepsy, or SUDEP).

Prognostication of outcome after cardiac arrest and targeted temperature management

The vast majority of cardiac arrest (CA) survivors remain comatose at hospital arrival. Around one-half of these patients suffer from severe hypoxic encephalopathy leading to death or unresponsive wakefulness. Early outcome prognostication may reduce futile intensive care and suffering for next of kin. Several early prognostic markers have shown high positive predictive value for poor outcome in patients treated at normothermia, but results may be altered by targeted temperature management (TTM). Most prominently, absent motor response to painful stimuli 3 days after CA and a serum concentration of neuron-specific enolase (NSE) above 33 ng/ml do not predict poor outcome reliably in these patients [1,2]. Sedation during TTM is a relevant confounder for motor response and corneal reflexes [3]. Bilaterally absent pupillary light reaction 3 days after CA is a reliable predictor of poor outcome (sensitivity 20%) [1]. Eye diseases and medication are potential confounders. A threshold for poor outcome prediction by NSE has not been established after TTM. Above a level of 80 to 100 ng/ml 72 hours after CA good outcome has rarely been reported. The NSE levels may vary with different test kits, and NSE producing tumors, acute brain diseases and severe hematological diseases/hemolysis are confounders. Bilateral absence of cortical median nerve SSEP remains a reliable predictor, but single cases with recovery were reported [4] and inter-rater reliability is not perfect. Preserved spinal SSEP and low cortical noise levels are important prerequisites. The sensitivity of absent SSEP for poor outcome prediction is around 40% [1]. EEG can be a valuable predictive tool when interpreted by experienced neurophysiologists and indicates (subclinical) status epilepticus [5]. The influence of medication on EEG needs to be considered. Recently, a revised EEG classification has been proposed [6]. A reduced contrast between gray and white matter in brain computed tomography is associated with poor outcome. It can be quantified as gray–white-matter ratio and values below 1.1 predict poor outcome with high specificity [7]. Additional studies are needed to establish this threshold more firmly. MRI emerges as a prognostic parameter because of high spatial resolution and high sensitivity for cytotoxic brain edema with DWI/ADC imaging [8]. However, access is limited and quantification of early changes needs to be established in larger cohorts. To date, most authors argue for a multiparameter prognostication approach including repeated neurological examination, SSEP, NSE, EEG and imaging (CT or MRI) combined with a waiting period for potential recovery of several days after cardiac arrest.

Infraslow Status Epilepticus: A new form of subclinical status epilepticus recorded in a child with Sturge Weber Syndrome

Background: Analysis of infraslow EEG activity (ISA) has shown potential in the evaluation of patients with epilepsy and in differentiating between focal and generalized epilepsies. The purpose of this report is to present a girl with Sturge-Weber Syndrome (SWS) who was identified to have infraslow status epilepticus (ISSE), which successfully resolved after Midazolam administration Methods: The continuous EEG recording of a 5-yr-old girl with known Structural Epilepsy due to Sturge-Weber is presented. The patient presented to the ED with acute confusion, eye deviation and right hemiparesis similar to two previous admissions. ltm-eeg showed diffuse slowing. DWI obtained within 72-hr showed no ischemic changes, analysis of the EEG nfraslow (ISA) activity was undertaken using LFF 0.01 AND HFF of 0.1 Hz respectively. Results: Continuous subclinical unilateral rhythmic ictal ISA was identified. This was only evident in the left hemisphere which correlated with the structural changes due to SWS. A trial of continuous IV midazolam resulted in immediate resolution of the contralateral hemiparesis and encephalopathy. Conclusion: Continuous prolonged rhythmic ictal Infraslow activity (ISA) can cause super-refractory subclinical focal status epilepticus. This has not previously reported, and we propose this should be called Infraslow status epilepticus (ISSE). ISA analysis should be performed in all patients with unexplained subclinical status epilepticus.

SIRPIDs

To determine the prevalence, associated factors, and outcomes of critically ill patients with stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs) on long-term video-EEG (VEEG). After IRB approval, we retrospectively reviewed patient characteristics and VEEG findings of all consecutive critical care unit patients who underwent VEEG monitoring between January 2012 and September 2012. The prevalence of SIRPIDs was 12.1% (4 of 33 patients; exact 95% confidence interval, 3.4%-28.2%). Factors associated with SIRPIDs versus non-SIRPIDs patients included a higher prevalence of subclinical status epilepticus (100% vs. 17.2%, P = 0.003), longer total VEEG recording time (286 vs. 56.9 hours, P = 0.0004), and acute traumatic brain injury (75.0% vs. 17.2%, P = 0.036). Sex, age, a history of epilepsy, nonstatus epileptic seizures, other EEG periodic patterns, and background rhythm reactivity on VEEG did not correlate with the presence of SIRPIDs. The presence or absence of SIRPIDs had no bearing on outcome; however, the population studied was very small. This small series suggests that the presence of subclinical status epilepticus and traumatic brain injury correlated with the presence of SIRPIDs signifying that SIRPIDs may be due to a more focal etiology and may represent a more ictal pattern than previously thought. Longer recording times in those patient populations may yield more cases of SIRPIDs in which to base further studies.

Severe cerebral injury in a recipient with twin anemia-polycythemia sequence

Twin anemia-polycythemia sequence (TAPS) results from slow intertwin blood transfusion through minuscule placental vascular anastomoses and is characterized by large intertwin hemoglobin differences in the absence of amniotic fluid discordance. The optimal management of TAPS is not clear. We report a case of TAPS detected antenatally by Doppler ultrasound examination at 15 + 6 weeks' gestation. After counseling, the parents opted for expectant management. Regular Doppler measurements were performed and these remained fairly stable. An emergency Cesarean section was performed at 34 + 5 weeks following signs of fetal distress. The donor twin was severely anemic while the recipient twin had severe polycythemia-hyperviscosity syndrome. On day 1, the recipient developed respiratory insufficiency and subclinical status epilepticus. Magnetic resonance imaging showed a total loss of gray-white matter differentiation as a sign of severe diffuse cerebral ischemia and bilateral intra- and extra-axial hemorrhages. There was almost complete lack of arterial and venous cerebral blood flow. On day 3 intensive care treatment was withdrawn in view of the severity of the brain injury. This case report demonstrates that TAPS may lead to severe cerebral injury and fatal outcome in the recipient twin, and highlights the importance of antenatal Doppler ultrasound monitoring and choice of management.

Diminished Visibility of Cerebral Venous Vasculature in Subclinical Status Epilepticus by Susceptibility-Weighted Imaging: A Case Report

Diminished Visibility of Cerebral Venous Vasculature in Subclinical Status Epilepticus by Susceptibility-Weighted Imaging: A Case Report

Common Errors Made in the Diagnosis and Treatment of Epilepsy

Learning from one's mistakes is the best learning tool in medicine and this applies as well to epilepsy. This article is a compilation of some of the frequent mistakes that are made in the evaluation and management of patients with epilepsy. It encompasses errors in the clinical diagnosis that result in the choice of the erroneous antiepileptic drug (AED), errors in the way auxiliary tests like the electroencephalogram and magnetic resonance imaging studies are ordered, mistakes in the recognition of subclinical status epilepticus, errors in the selection of AEDs, consequences of the failure to factor in the pharmacokinetic and pharmacodynamic properties of AEDs in the choice and dosification of medication, misconceptions on the expectations of therapeutic effect of AEDs, delay in recognition of refractory epilepsy with consequent delay in a timely identification of patients whose epilepsy can be cured with surgical treatment, and mistakes in the recognition and management of comorbid psychiatric disorders. In addition to a discussion of the reasons for the errors, the article provides practical solutions.

Status Epilepticus in the Pediatric Emergency Department

Status epilepticus (SE) is a common childhood condition often seen by emergency physicians. It occurs at a frequency of between 17 and 23 per 100 000, higher in younger children. Risk factors for SE include an acute symptomatic etiology, and for those children with underlying epilepsy, a remote symptomatic etiology and a younger age of epilepsy onset. Treatment paradigms vary by institution but should be rapid and aggressive. Underdosing of anticonvulsants and excessive lag between doses should be avoided. Identification of nonconvulsive and subclinical SE is often missed and requires a high index of suspicion. Refractory SE often requires an intensive care unit admission and the involvement of a neurologist. Etiologic evaluation should include a broad differential and be focused initially on treatable causes, including central nervous system infections, electrolyte and metabolic disorders, and trauma.

Ketamine for refractory status epilepticus: a case of possible ketamine-induced neurotoxicity

A 44-year-old man with treated neurosyphilis presented with subclinical status epilepticus (SE) refractory to intravenous high-dose lorazepam, phenytoin, and valproic acid over 4 days. Ketamine infusion was instituted after low-dose propofol sedation with gradual control of electrographic seizures over 72 h. Reevaluation 3 months later revealed diffuse cerebellar and worsened cerebral atrophy, consistent with animal models of N-methyl- d-aspartate antagonist-mediated neurotoxicity. Animal studies of prolonged ketamine therapy are required before widespread human use in SE.

Clinical Experience of Three Pediatric and One Adult Case of Spike-and-Wave Status Epilepticus Treated With Injectable Valproic Acid

Subclinical or nonconvulsive status epilepticus may cause severe postmorbid neurologic dysfunction. It is, therefore, critical to rapidly identify and treat these cases. The recent availability of injectable valproic acid (Depacon) provides an additional method for treatment of status epilepticus, although studies concerning its effectiveness are not widely available in the literature. We report four cases (three pediatric, one adult) of patients who presented to us in status epilepticus. All had previously failed more than one other common method of treatment for this condition. Treatment with injectable valproic acid resulted in the elimination of all clinical indications of status epilepticus as well as a return to the baseline EEG condition in all four cases. Seizure types included focal, multifocal, and generalized spike and wave forms, suggesting potential benefit from injectable valproic acid treatment in a wide range of status epilepticus patients. We present these cases for review.

Serum neuron-specific enolase in the major subtypes of status epilepticus.

To determine the relative magnitudes of neuron-specific enolase (NSE) levels after complex partial status epilepticus (SE), absence SE, generalized convulsive SE, and subclinical generalized convulsive SE (frequently referred to as acute symptomatic myoclonic status epilepticus). NSE is a marker of acute brain injury and blood-brain barrier dysfunction, which is elevated in SE. Serum NSE levels were drawn in 31 patients 1, 2, 3, and 7 days after SE. Patients were classified as acute symptomatic or remote symptomatic, and the duration and outcome of SE were determined and correlated with the peak NSE level. NSE was elevated significantly in all four subtypes of SE, but NSE levels were highest in complex partial and subclinical SE. The mean peak NSE level for the complex partial SE group was 23.88 ng/mL (n = 12), 21.5 ng/mL for absence SE (n = 1), 14.10 ng/mL for the generalized convulsive SE group (n = 12), and 37.83 ng/mL for the subclinical SE group (n = 6), all of which was significantly higher than normal control subjects (5.02 ng/mL). Outcome was significantly different between the three groups (p = 0.0007), and was significantly worse for subclinical SE (p = 0.0005, subclinical versus generalized convulsive SE). Serum NSE levels were highest in complex partial and subclinical generalized convulsive SE. The extremely high levels of NSE in subclinical SE reflect the severity of the acute neurologic insults and poor outcome common to subclinical SE. High NSE levels in complex partial SE reflects the long duration of SE in this subgroup, and potential for brain injury.

Clinical significance and outcome of subclinical status epilepticus in adults

We reviewed the medical records and the EEGs of all adults treated for status epilepticus (SE) in our center in 4 years. EEG detected subclinical SE in almost half (49%) of the 45 consecutive patients identified. Comparing patients with and those without subclinical SE, we noted that patients with subclinical SE were older ( p = 0.02) and more likely to have focal brain lesions ( p = 0.04). In the absence of focal brain lesions, subclinical SE was still more common in old adults ( p < 0.01). Regardless of age, subclinical SE was more difficult to control than clinically overt SE ( p = 0.001). Although 24% of all patients died in ⩽60 days, late mortality was not associated with subclinical SE ( p > 0.05). However, an association between late mortality and presence of focal brain lesions was suggested by a low p-value (0.053). Subclinical SE appeared on the EEG as frequent discrete seizure episodes in all but 3 patients. None of the patients had a progressive sequence of EEG patterns, as was reported in the literature. Initiation of treatment before EEG recording in most of our patients (82%) might have interrupted the sequential appearance of the EEG patterns.

Adrenergic crisis from crack cocaine ingestion: Report of five cases

We report the historical, clinical, and laboratory findings in 5 patients after crack cocaine ingestion. All patients exhibited adrenergic crisis as a result of their ingestion. Analysis of their history revealed a latency period before signs and symptoms occurred as well as a wide variation in the number of crack cocaine nuggets ingested. Signs of intoxication were hypertension, tachycardia, hyperthermia, agitation, and generalized seizure activity. Treatment included therapeutic sedation with lorazepam and adrenolysis with esmolol infusion. The majority of patients showed electrocardiographic evidence of cardiac ischemia, but not elevations in serum creatinine phosphokinase enzymes-MB fraction. One patient died of complications associated with subclinical status epilepticus. The toxicities of crack cocaine ingestion are seldom appreciated. Prompt reversal of both cardiovascular and neurological signs and symptoms with appropriate pharmacologic agents is indicated.